Primary Lung Squamous Cell Carcinoma With Intestinal Metastasis: A Case Report and Literature Review

ABSTRACT Lung squamous cell carcinoma (LUSC) is characterized by a high rate of metastasis and recurrence, leading to a poor prognosis for affected patients. Intestinal metastasis of LUSC is a rare clinical occurrence. Treatment options for LUSC patients with intestinal metastasis are limited, and no standard therapy guidelines exist for managing these cases. In this review, we discuss the clinical features, diagnosis, and treatment of LUSC patients with intestinal metastasis and present a rare case of LUSC with intestinal metastasis. We describe a patient who presented with a severe cough and chest pain and diagnosed with LUSC and bone tumor. Initially, the primary LUSC and bone tumor were controlled with standard treatments. However, the primary LUSC reoccurred shortly after treatment, this time with intestinal metastasis, for which effective treatments are lacking. Our observation from the case suggests that LUSC metastasizing to intestinal tract is associated with a poorer prognosis.


| Introduction
Lung squamous cell carcinoma (LUSC), accounting for 20%-30% of non-small cell lung cancer (NSCLC) cases, is associated with high mortality rates [1].In its early stages, LUSC symptoms are mild and are often go unnoticed.Consequently, most patients are diagnosed at an advanced stage [2].Intestinal metastasis from lung cancer is a relatively rare, and its clinical diagnosis primarily relies on imaging examinations [3].In this review, we discuss the clinical features, diagnosis, and treatment of LUSC patients with intestinal metastasis and present a rare case of LUSC accompanied by intestinal metastasis.

| Case Presentation
A 55-year-old male presented with a severe cough accompanied by chest pain and was diagnosed with lung cancer in the right hilum of the lung (Figure 1A) and a tumor in the left femur (Figure 1B) at our hospital on January 6, 2023.The patient had a history of smoking, beginning at Age 10, with consumption gradually increasing from 10 to 20 cigarettes per day until he quit smoking in June 2022.He also began drinking alcohol at the age of 21, with intake progressively increasing to 350 mL (52%, v/v) per day, and ceased alcohol consumption in December 2022.Between 1997 and 2004, he worked in a coal mine, where he was chronically exposed to dust and other toxic and harmful gases.In 2003, he started experiencing symptoms of a dry cough without expectoration or hemoptysis, which exacerbated annually for at least 3 months each year.Despite these symptoms, he had never sought medical attention or treatment prior to the lung cancer diagnosis.A pathological biopsy confirmed the primary lung cancer as poorly differentiated LUSC with the following immunohistochemical profile: TTF1 (−), NaspinA (−), CK7 (−), CgA (−), p63 (−), p40 (+), p63 (+), CK5/6 (+), and Ki67 (+) (Figure 2).We administered the standard chemotherapy regimen for primary squamous lung cancer: paclitaxel (300 mg i.v.gtt qd) combined with cisplatin (120 ng i.v.gtt qd).After twocycle chemotherapies on January 17, 2023, and February 7, 2023, the patient's cough symptoms were alleviated, and the primary lesion significantly reduced in size.Due to femoral pain caused by the femoral tumor, the patient received radiotherapy in the Oncology Department of our hospital on March 17, 21, and 27, 2023.
During radiotherapy, we detected the expression of PDL1 and CD8 in LUSC samples using immunohistochemistry.We found that almost all LUSC cells expressed PDL1, while only a few cells expressed CD8 (Figure 2I,J).Consequently, we administered immune checkpoint inhibitors to the patient three times: Svolumab 300 mg (March 8, 2023), Svolumab 120 mg (March 16, 2023), and Svolumab 300 mg (March 29, 2023).Following these treatments, the patient's femoral pain was alleviated.However, a subsequent chest CT scan revealed that the primary lung tumor had increased in size compared to the scan from January 6, 2023.We recommend chemotherapy combined with immunotherapy (tirellizumab 200 mg and carboplatin 600 mg) on April 21, 2023.Unexpectedly, on June 1, 2023, the patient experienced repeated difficulty with defecation.Colonoscopy and laparoscopy revealed nodular eminence in transverse colon (Figure 3A,B).Pathological results confirmed squamous cell carcinoma, likely originating from the lung: CDX-2 (−), CK7 (−), CK20 (−), p63 (+), p40 (+), CK5/6 (+), and Ki67 (+) (Figure 3C-J).To address the defection issues, a transverse colostomy was performed in the Gastroenterostomy Department of our hospital on June 30, 2023.Extensive abdominal malignant tumor metastasis was discovered during the operation.The surgery was uneventful, and the patient experienced relief from postoperative abdominal pain.However, due to reliance solely on parenteral nutrition postsurgery, the patient's vital signs deteriorated, and he developed cachexia.One week later, the patient's abdominal pain recurred, and he developed nausea and vomiting after eating.He was transferred to the Oncology Department for further treatment.Over the following month, the patient experienced upper gastrointestinal bleeding and jaundice.Imaging studies indicated extensive tumor progression, and the patient entered the cachectic phase of malignant tumors.Palliative care was planned, and after discussions with the patient and his family, he refused inhospital palliative treatment and requested to be discharged.No further treatment was administered subsequently.

| Discussion
The probability of gastrointestinal metastasis from lung cancer varies from 4.7% to 14% [4][5][6][7][8][9][10][11][12][13][14][15].This reports a rare case of LUSC with metastasis to both intestines and bones.Unfortunately, the patient had bone metastases and was not a candidate for surgery at the time of diagnosis.Consequently, we relied on immunotherapy, chemotherapy, and radiotherapy to manage the condition and alleviate pain.In this study, we administered the standard chemotherapy regimen for primary LUSC, supplemented with immunotherapy and radiotherapy for bone tumors.Following these treatments, the disease was controlled to some extent, and the patient's quality of life improved.However, the primary lesion soon became uncontrolled again, now accompanied by intestinal metastasis.This development suggests that LUSC patients with intestinal metastasis have a poorer prognosis when treated with standard therapy regimens [16,17].Therefore, it is imperative to explore more therapeutic methods and effective regimens urgently.
Unlike LUAD, LUSC lacks effective molecular targets, making targeted therapies rare for LUSC [18][19][20].Differentiating LUSC from LUAD is crucial for selecting appropriate drug during lung cancer treatment.However, treatment options for first-line therapy of advanced LUSC remain limited compared to other types

FIGURE 1 |
FIGURE 1 | Enhanced computed tomography (CT) scans.(A) Chest scans indicated the presence of a right hilum nodule in the lung.(B) Leg scans showed tumor infiltration in the femur.

TABLE 1 |
[16,17,21]usly reported lung squamous cell carcinoma with intestinal metastasis.Patients with advanced LUSC primarily benefit from radiotherapy, chemotherapy, or immunotherapy.Platinumbased chemotherapies are the main regimens for advanced LUSC and can effectively improve overall survival.Unfortunately, rare cases with intestinal metastasis have a worse outcome, with an overall survival of only 4-8 weeks[16,17,21].Table1summarizes previous reports on therapies for intestinal metastasis of LUSC.All patients received radiotherapy, chemotherapy, or surgery for gastrointestinal tumors after the onset of gastrointestinal symptoms, but no standard treatment exists for LUSC with gastrointestinal metastasis.Most cases involved symptomatic treatment to improve quality of life and relatively prolong survival time.Recently, some clinical trials (RATIONALE 307 and ORIENT-12) have shown that patients with advanced squamous NSCLC benefit from immunotherapies.However, in this case, the patient's symptoms did not significantly improve after immunotherapy, indicating that further development and improvement of immunotherapy are needed.